Androgen and oestrogen receptors as potential prognostic markers for patients with ductal carcinoma in situ treated with surgery and radiotherapy

Abstract

Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has been investigated less extensively than invasive breast cancer. Women with DCIS are mainly treated with conservative surgery almost exclusively followed by radiotherapy. However, as radiation treatment is not always effective, the search for biomarkers capable of identifying DCIS lesions that could progress to invasive cancer is ongoing. Although conventional biomarkers have been thoroughly studied in invasive tumours, little is known about the role played by androgen receptor (AR), widely expressed in DCIS. A series of 42 DCIS patients treated with quadrantectomy and radiotherapy were followed for a period of up to 95 months. Of these, 11 had recurrent DCIS or progressed to invasive cancer. All tumours were analysed for clinical pathological features. Conventional biomarkers and androgen receptor expression were determined by immunohistochemistry. Our results showed that AR was higher in tumours of relapsed patients than non-relapsed patients (P value: 0.0005). Conversely, oestrogen receptor (ER) was higher, albeit not significantly, in non-relapsed patients than in relapsed patients. AR/ER ratio was considerably different in the two subgroups (P value: 0.0033). Area under the curve (AUC) values were 0.85 for AR and 0.80 for the AR/ER ratio. These preliminary results highlight the potentially important role of both AR and the AR/ER ratio as prognostic markers in DCIS.

Androgen Receptor in Breast Cancer—Clinical and Preclinical Research Insights

“…A retrospective analysis of 42 Ductal Carcinoma in situ of the breast (DCIS) patients treated with surgery followed by radiotherapy showed that AR expression was considerably higher in relapsed tumors (p = 0.0005), whereas ERα was higher in non-relapsed ones. The AR:ERα ratio was different among the subgroups (p = 0.0033), indicating the unfavorable prognostic role of AR and AR/ERα in this subset of patients [21]. Consistently, another study revealed that the AR:ERα value could be used as a highly specific and sensitive prognostic tool for in situ relapse or progression to invasive subtypes [22].…”

The impact of androgen receptor (AR) and histone deacetylase 1 (HDAC1) expression on the prognosis of ductal carcinoma in situ (DCIS)

“…Other studies showed that AR expression level was higher in DCIS adjacent to IDC compared to pure DCIS [20,21]. In statistical analyses of the expression of several biomarkers of breast cancer, AR did not show statistical signi cance as a risk factor for recurrence [22].Recently, based on the concept of competition between AR and ER, Ravaioli et al suggested AR/ER ratio as a prognostic marker for DCIS [23]. AR indeed was associated with a favorable prognosis in this study population which correlates with the previously reported biological effect of AR as an ER signal inhibitor.…”

Evaluation of Androgen Receptor in Relation to Estrogen Receptor (AR/ER) and Progesterone Receptor (AR/PgR): A New Must in Breast Cancer?

“…We previously demonstrated an unfavorable prognostic role of the AR/ER ratio in different subsets of patients (i.e., patients with ductal carcinoma in situ of the breast), independently of treatment ( i.e. , surgery alone or surgery plus radiotherapy) [12–14]. Similarly, Rangel et al and Cochrane et al reported a poorer prognosis when the AR/ER ratio was higher in the primary tumor of early BC patients [9, 10].…”

“…Given that we aimed to calculate the AR/ER and AR/PgR ratios, AR expression value was considered as a continuous variable (percentage of immunopositive tumor cells ranging 0-100%) and not dichotomous (positive/negative). As reported in our previous work, when ER or PgR were negative, the AR value was used instead of AR/ER and AR/PgR values [12].…”